Olanzapine, Samidorphan Prove Effective in Treating Bipolar 1 Disorder, Schizophrenia

Olanzapine and samidorphan proved effective in treating bipolar 1 disorder (BD-1) and schizophrenia while mitigating weight gain that is associated with just taking olanzapine, according to the results of a review published in Neuropsychiatric Disease and Treatment.

Olanzapine is highly effective in helping stabilize individuals with BD-1 and schizophrenia, but it also affects how the body regulates glucose and lipids.

The natural opioid system regulates metabolism and weight changes, so combining olanzapine and samidorphan, an opioid receptor-blocking compound, is a potential strategy for addressing the drug-associated weight gain, investigators said.

In the review, investigators compared the use of olanzapine and samidorphan with just olanzapine and a placebo for individuals with acute exacerbation of schizophrenia. They found that the combination and olanzapine alone provided similar improvements at week 4 compared with the placebo, which was measured by Positive and Negative Syndrome Scale (PANSS) scores from the baseline.

The antipsychotic efficacy of the drug combination compared with the placebo was supported by improved Clinical Global Impression-Severity (CGI-S) scores. The addition of samidorphan did not negatively affect the antipsychotic efficacy of olanzapine.

In the ENLIGHTEN-2 (NCT02694328)study, treatment improvement was similar between the 2 groups in PANSS and CGI-S scores.

In outpatient individuals with stable schizophrenia, treatment with the combination resulted in significantly less weight gain. Additionally, it reduced the risk of clinically significant weight gain, and waist circumference increased by 5 cm or more by up to half compared with olanzapine alone at week 24.

Investigators of the ENLIGHTEN-2 study found that the least squares mean percent weight change from the baseline to the end of the treatment period at 24 weeks was 4.2% with the drug combination compared with 6.6% with olanzapine alone. In a phase 2 study, the least squares mean percent change from the baseline in weight at 12 weeks was 2.6% for the combination compared with 4.1% for olanzapine alone.

In both studies, individuals treated with either regimen had similar weight gain for the first 4 to 6 weeks. However, those treated with the combination had their weight stabilize, while those treated with olanzapine alone continued to gain weight throughout the treatment period.

Furthermore, investigators found that, in the ENLIGHTEN-2 study, the risk of gaining 10% or more of body weight from the baseline was reduced by 50% when individuals took the combination compared with olanzapine alone.

The investigators found that the combination of olanzapine and samidorphan is safe and well tolerated for up to 3 and a half years of treatment. The combination helped maintain symptoms and stabilize their weight. They also found that the combination did not affect lithium or valproate pharmacokinetics.

In the review, investigators summarized clinical data from 18 studies, including 10 phase 1 trials, 2 phase 2 trials, 3 double-blinded, randomized phase 3 trials, and 3 long-term, open-label, phase 3 extension studies.

They used these data to evaluate the efficacy, pharmacokinetics, and safety of the drug combination.

The FDA recently approved olanzapine and samidorphan as a treatment for BD-1 and schizophrenia.

Reference

Citrome L, Graham C, Simmons A, Jiang Y, et alt. An evidence-based review of OLZ/SAM for treatment of adults with schizophrenia or bipolar I disorder. Neuropsychiatr Dis Treat. 2021;17:2885-2904. doi:10.2147/NDT.S313840